1. Field of the Invention
The present invention relates generally to the field of chemistry and oncology. More specifically, the invention relates to new compounds that were isolated from soybeans as well as methods for the use thereof
2. Description of Related Art
Numerous compounds isolated from plants have been investigated for biological properties. For example, triterpene saponins have been identified with fungicidal, anti-viral, anti-mutagenic, spermicidal or contraceptive, cardiovascular, and anti-inflammatory activities (Hostettmann et al., 1995). Saponins are known to form complexes with cholesterol by binding plasma lipids, thereby altering cholesterol metabolism (Oakenfull et al., 1983). Triterpene glycosides given in feed also have been shown to decrease the amount of cholesterol in the blood and tissues of experimental animals (Cheeke, 1971).
Soybeans, and processed soy products containing isoflavonoids and saponins in particular are of wide interest for their multifaceted biological effects (Messina, 1999; Messina et al., 1994; Merz-Demlow et al., 2000; Setchell, 1998). Isoflavone, cinnamic acid and triterpenoid glycoside compounds have been isolated from soybean molasses, a concentrate of the aqueous extract prepared during the processing of soybeans (Hosny and Rosazza, 1999). A soybean phytochemical concentrate (SPC) comprising a powdered proprietary concentrate prepared from soybeans (Glycine max L. Merr.) has been described by Archer Daniel Midland Co. (Zhou et al., 1999). SPC contains 40–50% (w/w) of soy isoflavones with a profile of components that matches those found in tofu, the most commonly consumed soy food (Tezuka et al., 2000). The principal known isoflavones in SPC are daidzein-7-O-β-D-(6″-O-acetylglucopyranoside), and genistein-7-O-β-D-(6″-O-acetylglucopyrano-side) along with daidzein, genistein, glycitein and their respective β-glucosides daidzin, genistin and glycitin. While the overall composition of SPC is similar to that of soybean molasses, SPC also contains different isoflavonoid components (Hosny and Rosazza, 1999; Zhou et al., 1999) and soy saponins, plus a variety of very minor components, all of which are found naturally in soybeans.
Several investigations have shown that soy isoflavonoids, particularly genistein, inhibit the proliferation of transformed cells in culture (Arao et al., 1997) and some in vivo studies (Rao et al., 1997) report that pure isoflavones or dietary soy protein inhibit tumorigenesis in rodent models (Hawrylewicz et al., 1995). Genistein is a naturally occurring isoflavonoid isolated from soy products that is a known tyrosine kinase inhibitor shown to inhibit the proliferation of estrogen-positive and estrogen-negative breast cancer cell lines (Akiyama et al., 1987).
Different mechanisms may be implicated for such biological activities including: agonist/antagonist effects on estrogen receptors (Adlercreutz et al., 1995), stimulation of sex hormone-binding globulin synthesis (Adlercreutz et al., 1995), inhibition of growth factor-associated tyrosine-kinase signal transduction (Akiyama et al., 1987), antioxidant properties (Naim et al., 1976), and inhibition of DNA topoisomerase (Okura et al., 1988). Although such studies are highly suggestive of the beneficial effects of soy consumption in general with regard to cancer prevention, definitive intervention trials have not been completed. In contrast, others have shown that particular soybean components do not inhibit tumorigenesis (Messina et al., 1994). Consumption of a soybean-based diet (McIntosh et al., 1995) or administration of genistein (Rao et al., 1997) resulted in increasing colon tumor incidence and tumor burden in rats treated by chemical carcinogens. Further, it has been hypothesized that the estrogenic properties of certain soy isoflavones may stimulate breast tumor growth under some conditions (Peterson and Barnes, 1991)
One triterpene known to have biological activity is glycyrrhetinic acid. This compound and certain derivatives thereof have been shown to have anti-ulcer, anti-inflammatory, anti-allergic, anti-hepatitis and antiviral actions. For instance, certain glycyrrhetinic acid derivatives can prevent or heal gastric ulcers (Doll et al., 1962). Among such compounds known in the art are carbenoxolone (U.S. Pat. No. 3,070,623), glycyrrhetinic acid ester derivatives having substituents at the 3′ position (U.S. Pat. No. 3,070,624), amino acid salts of glycyrrhetinic acid (Japanese Patent Publication JP-A-44-32798), amide derivatives of glycyrrhetinic acid (Belgian Patent 753773), and amide derivatives of 11-deoxoglycyrrhetinic acid (British Patent 1346871). Glycyrrhetinic acid has been shown to inhibit enzymes involved in leukotriene biosynthesis, including 5-lipoxygenase activity, and this is thought to be responsible for the reported anti-inflammatory activity (Inoue et al., 1986).
Betulinic acid, a pentacyclic triterpene, is reported to be a selective inhibitor of human melanoma tumor growth in nude mouse xenograft models and was shown to cause cytotoxicity by inducing apoptosis (Pisha et al., 1995). A triterpene saponin from a Chinese medicinal plant in the Cucurbitaceae family has demonstrated anti-tumor activity (Kong et al., 1993). Monoglycosides of triterpenes have been shown to exhibit potent and selective cytotoxicity against MOLT-4 human leukemia cells (Kasiwada et al., 1992) and certain triterpene glycosides of the Iridaceae family inhibited the growth of tumors and increased the life span of mice implanted with Ehrlich ascites carcinoma (Nagamoto et al., 1988). A saponin preparation from the plant Dolichos falcatus, which belongs to the Leguminosae family, has been reported to be effective against sarcoma-37 cells in vitro and in vivo (Huang et al., 1982). Soya saponin, also from the Leguminosae family, has been shown to be effective against a number of tumors (Tomas-Barbaren et al., 1988).
While previous studies have identified compounds which have any of a number of uses, there still is a great need in the art for the identification of novel biologically active compounds. Prior compounds may be toxic to normal cells or possess other undesirable characteristics or may have limited or varying degrees of biological activity. Therefore, identification of new compounds may provide new routes of treating a variety of conditions, thereby avoiding the shortcomings of the prior art.